MALE-PREFERENCE FOR THE ODORS OF ESTROUS FEMALE MICE IS ENHANCED BY THE NEUROSTEROID 3-ALPHA-HYDROXY-4-PREGNEN-20-ONE (3-ALPHA-HP)

The effects of the centrally produced allylic neurosteroid, 3 alpha-hy droxy-4-pregnen-20-onc (3 alpha HP), on the responses of male mice to the odors of estrous female mice were examined in an odor preference t est. Control untreated mice displayed a significant preference for the odors of an estrous female, spending more time in a Y-maze in the vic inity of the odors of an estrous than a non-estrous female. Intracereb roventricular (i.c.v.) administrations of 3 alpha HP enhanced male pre ference for the odors of estrous females, causing a significant dose-r elated (0.01-1.0 mu g) increase in the amount of time spent in the pro ximity of the odors of the estrous female, while having no significant effect on the responses to the non-estrous female odors. These effect s of 3 alpha HP were stereospecific, with the stereoisomer, 3 beta-hyd roxy- 4-pregnen-20-one (3 beta HP), having no significant effects on o dor preferences. The analgesic, morphine, also had no significant effe cts on the responses to female odors suggesting that the enhanced pref erence for estrous female odors were unlikely to be directly due to an y analgesic effects of 3 alpha HP. The effects of 3 alpha HP were sign ificantly reduced by peripheral administrations of the GABA, antagonis ts, bicuculline and picrotoxin, but were unaffected by either the benz odiazepine antagonist, Ro 15-1788, or the opiate antagonist, naloxone. These results suggest that the neurosteroid 3 alpha HP has facilitato ry effects on olfactory mediated male sexual interest or motivation th at involve interactions with the GABA(A) receptor.